Biofungsi

Sinapsis Oleh:
Heru
Nurcahyo

Program
Pascasarjana
UNY

2016
SINAPSIS
• Sinapsis adalah hubungan antara neuron satu
dengan lainnya (Sherrington)
• Sinapsis secara struktural tersusun atas:
1.Membran presinaptik
2.Celah sinapsis
3.Membran postsinaptik.
• Neurotransmitter:
• Asetilkolin (ACh)
• Norepinefrin (NE) atau noradrenalin (NA)
• Epinefrin (adrenalin)
 Synapse
• Functional connection between a
neuron and another cell.
• Different types of synapses involve:
– Axodendritic (b):
• Axon of one neuron and dendrite of
another neuron.
– Axosomatic (a):
• Axon of one neuron and cell body of
another neuron.
– Axoaxonic (c):
• Axon of 1 neuron and axon of another
neuron.
• Transmission in one direction only.
Two types of synapses for transmit information between neurons
1. Electrical synapse
2. Chemical synapse
Electrical synapses

At electrical synapses, the presynaptic cell and postsynaptic cell are

connected by protein complexes called gap junctions, which are made of of
subunits called connexins.

Electrical synapses provide rapid and faithful signal transmission between

cells, but a less flexible response than chemical synapses.
 Electrical Synapse
• Impulses can be
regenerated without
interruption in adjacent
cells.
• Gap junctions:
– Adjacent cells
electrically coupled
through a channel.
• Examples:
– Smooth and cardiac
muscle.
– CNS, retina
 Chemical Synapse

• Presynaptic terminal (bouton) releases

a chemical (neurotransmitter).
• Synaptic transmission is through a
chemical gated channel.
 Chemical Synapse
• Terminal bouton is
separated from
postsynaptic cell by
synaptic cleft.
• Neurotransmitters (NT)
are released from synaptic
vesicles.
• Amount of
neurotransmitter released
depends upon frequency
of AP.
 Synaptic Transmission

• AP travels down axon to bouton.

• VG Ca++ channels open.
• Ca++ enters bouton down concentration
gradient.
• Ca++ activates calmodulin, which activates
protein kinase.
 Synaptic Transmission

• NT is released and diffuses across synaptic

cleft.
• Neurotransmitter (ligand) binds to receptor
in postsynaptic cell.
• Chemical gated ion channel opens.
• EPSP: depolarization.
• IPSP: hyperpolarization.
• Neurotransmitter inactivated.
Chemical synapses

Signals are carried across the synaptic cleft between the presynaptic and
postsynaptic cells by the diffusion of neurotransmitter molecules.

Fast direct chemical synapses: the transmitter receptor proteins include the
both the binding site for the transmitter and an ion channel.
Neurotransmitters are synthesized in the axon terminals and stored in small
vesicles. These transmitters are typically small organic molecules.
Slow indirect chemical synapses: the transmitter receptor proteins act
through intracellular messenger systems to affect the conductance
through ion channels.
The transmitters are typically large molecules containing a single amino
acid (biogenic amines) or several amino acid residues (neuropeptide).
They are usually synthesized in the soma, packaged into large vesicles,
and transported to the axon terminal.
The onset of response is slower, but last longer (seconds to hours)
Excitatory postsynaptic potential (epsp)
A change in the membrane potential of a postsynaptic cell that increases the
probability of an action potential in that cell.

Inhibitory postsynaptic potential (ipsp)

A change in the transmembrane potential of a postsynaptic cell that reduces the
probability of an action potential in that cell.
Excitatory postsynaptic potential (epsp)
The current are typically carried through Na+ or Ca2+.

Inhibitory postsynaptic potential (ipsp)

The current are typically carried through channels that are permeable either to K + or to
Cl-.
 Synaptic Integration
• EPSPS can summate,
producing AP.
– Spatial summation:
• Numerous boutons
converge on a single
postsynaptic neuron
(distance).
– Temporal summation:
• Successive waves of
neurotransmitter
release (time).
 EPSP
• No threshold.
• Decrease resting
membrane potential.
– Closer to threshold.
• Graded in magnitude.
• Have no refractory
period.
• Can summate.
 IPSP
• No threshold.
• Hyperpolarize
postsynaptic membrane.
• Increase membrane
potential:
– Further away from
threshold.
• Can summate.
• No refractory period.
Excitation and inhibition depend critically on the nature of the local
ionic gradients (properties of the channel & identities of the ions that
flow) and not on the identity of the signaling molecule.
Presynaptic inhibition: Neuronal inhibition resulting from action of an inhibitory
terminal that synapses on the presynaptic terminal of an excitatory synapse,
which reduces the amount of transmitter released.
1. Increasing gk and gCl in the presynaptic terminals
2. Reducing Ca2+ entry in the presynaptic terminals
Neurotransmitter releasing depends on
• Depolarization of presynaptic membrane
• More depolarization caused more transmitter to be released
• Extracellular Ca2+ concentrations
Transmitter release steps
1. Mature vesicles move up to active zones with
assistance of cytoskeletal protein actin and
myosin.
2. Vesicle attached to membrane by the sec6/8
and rab proteins (reversible)
3. Attached irreversibly by forming SNARE complex
4. Synaptotagmin interacts with the SNARE
complex to produce rapid fusion.
 Classification of neurotransmitters
• Acetylcholine (ACh)
• Biogenic amines (norepinephrine, dopamine,
serotonin, histamine)
• Amino acids (r-aminobutyric acid, glutamate,
glycine)
• polypeptides (somatostatin, substance P,
LHRH)
• Novel messengers (ATP, NO, CO)
 Acetylcholine (ACh) as
Neurotransmitter
• ACh is both an excitatory and inhibitory
NT.
• Causes the opening/closing of chemical
gated ion channels.
 Ligand-Operated ACh Channels
• Most direct
mechanism.
• Ion channel runs
through receptor.
• Receptor has 5
polypeptide subunits
that enclose ion
channel.
• 2 subunits contain
ACh binding sites.
• Permits diffusion of
Na+.
 G Protein-Operated ACh
Channel
• Only 1 subunit.
• Ion channels are
separate proteins
located away from the
receptors.
• Binding of ACh
activates alpha G
protein subunit.
• Alpha subunit or the
beta-gamma complex
diffuses through
membrane until it
binds to ion channel,
opening it.
General events at G-protein coupled receptor
1. Neurotransmitter binds to the receptor protein
2. GDP is released from G subunit
3. GTP binds to the  protein cause dissociation of G-protein from the receptor and
 from  subunits
4. Activated  subunitor the beta-gama complex binds to the effector molecules
(signal transduction)
5. GTP was hydrolyzed to GDP by GTPase (termination of signal)
6. Bound to GDP again, the  and  form complex and bind to the receptor.
At least three separate proteins contribute to slow, indirect
chemical synaptic transmission
1. Neurotransmitter receptor protein (seven transmembrane domains)
2. Activated G proteins including  subunits or  comlex,
3. Effector proteins (ion channels, enzyme for 2 nd messenger)
G-proteins can function only if GTP is available
Nonhyrolyzable analog of GTP, GTPS induce stable activation of
the G protein.
 Acetylcholinesterase
• AChE:
• Enzyme that
inactivates ACh.
• Prevents
continued
stimulation.
 Monoamines as NT
• Monoamine NTs:
– Epinephrine
– Norepinephrine
– Serotonin
– Dopamine
• Released by exocytosis from presynaptic
vesicles.
• Diffuse across the synaptic cleft.
• Interact with specific receptors in
postsynaptic membrane.
 Mechanism of Action
• Monoamine NT do not
directly open ion channels.
• Act through second
messenger, cAMP.
• Binding of norepinephrine
stimulates dissociation of
G protein alpha subunit.
• Alpha subunit binds to
adenylate cyclase,
converting ATP to cAMP.
• cAMP activates protein
kinase, phosphorylating
other proteins.
• Reuptake of monoamines
into presynaptic
membrane.
• Enzymatic degradation in
presynaptic membrane by
MAO.
• Enzymatic degradation in
postsynaptic membrane
by COMT.
Terima Kasih

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